Normal Development - Milk

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A personal message from Dr Mark Hill (May 2020)  
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I have decided to take early retirement in September 2020. During the many years online I have received wonderful feedback from many readers, researchers and students interested in human embryology. I especially thank my research collaborators and contributors to the site. The good news is Embryology will remain online and I will continue my association with UNSW Australia. I look forward to updating and including the many exciting new discoveries in Embryology!

Introduction

Adult female mammary anatomy cartoon

Breast milk makes us mammals! This current page discusses some issues related to milk and neonatal nutrition, it is not a guide to breastfeeding, which is covered by many other resources. The composition of milk can vary over time, with colostrum the initial yellowish, sticky breast milk produced at the end of pregnancy.

The review article (abstract shown below) by Goldman in 2000[1] may provide a way of thinking about gastrointestinal tract and human milk.

There are other resource pages that cover the topic of breast development (More? mammary gland). Milk also has important role in gastrointestinal tract postnatal development (More? gastrointestinal tract)


Postnatal Links: birth | neonatal | neonatal diagnosis | milk | Nutrition | growth charts | Disease School Exclusion | vaccination | puberty | genital

| Nutrition

Some Recent Findings

  • The stepwise assembly of the neonatal virome is modulated by breastfeedingNature 15 April 2020 "Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 109 per gram, and these numbers seem to persist throughout life5,6,7. We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections8,9,10. Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells; this second phase is modulated by breastfeeding."
  • Human milk glycosaminoglycan composition from women of different countries: a pilot study[2] "In this pilot study, we report the composition, structure and properties of glycosaminoglycans (GAG) present in milk samples of various countries and ethnicities.Methods: Fifty samples of human milk were analyzed, 10 from east Europe, 10 from North Africa, 10 from Central Africa, 10 from South America and 10 from Asia. Moreover, 30 samples were obtained during the first week and 20 between 8 to 30 days of life. Overall, no significant differences were observed for the qualitative composition of GAGs, mainly chondroitin sulfate, heparan sulfate and hyaluronic acid, comparing the mothers from the various countries and between the 30 milks obtained during the first week and the 20 samples collected thereafter. Moreover, no significant differences in human milk GAGs within the different groups analyzed belonging to various counties and ethnicities were observed. These results may be of useful, as in the case of pilot studies with infant formulas enriched with chondroitin sulfate (CS) and/or heparan sulfate (HS) necessary to verify their possible positive effects on newborns feeding in countries at high risk of infection and/or infestation."

Mammary Glands Pregnancy

During pregnancy raised estrogens and progesterone stimulate gland development, secretory alveolar structures form and differentiate, leading to milk production in late pregnancy and milk secretion during lactation. Breasts are hemispherical in shape due to fat deposition. After birth, neonatal lactation supports further growth/development.


Links: Integumentary Development - Mammary Glands

Milk Composition

Hydrolysis of lactose

Most mammals produce milk containing similar components which may occur at different concentrations. Composition of the maternal diet can affect the concentration of some of these components. In addition, some materal environmental components can also appear in the milk.

Typical secreted milk contains:

  • Carbohydrate: lactose, glucose, galactose, and oligosaccharides
  • Electrolytes
  • Fats: triglycerides and fatty acids (omega-3 polyunsaturated fatty acids, such as docosahexanoic acid)
  • Minerals
  • Proteins: caseins, alpha-lactalbumin, immunoglobulins, albumin, lactoferrin, nonprotein nitrogen, enzymes, hormones, growth factors, and nucleotides
  • Trace elements: selenium and iodine
  • Vitamins: A, B1 (thiamin), B2 (riboflavin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), D, and E
  • Water

Lactoferrin

A bioactive protein in mammal milk with various neonatal actions, such as anti-infective, immunological, and gastrointestinal.[6]


Beta-lactoglobulin

Beta-lactoglobulin (β-lactoglobulin) is one of the most abundant milk whey proteins in many mammal species.


Human Milk

"Human milk contains agents that affect the growth, development and functions of the epithelium, immune system or nervous system of the gastrointestinal tract. Some human and animal studies indicate that human milk affects the growth of intestinal villi, the development of intestinal disaccharidases, the permeability of the gastrointestinal tract and resistance to certain inflammatory/immune-mediated diseases. Moreover, one cytokine in human milk, interleukin (IL)-10, protects infant mice genetically deficient in IL-10 against an enterocolitis that resembles necrotizing enterocolitis (NEC) in human premature infants.

There are seven overlapping evolutionary strategies regarding the relationships between the functions of the mammary gland and the infant’s gastrointestinal tract as follows:

  1. certain immunologic agents in human milk compensate directly for developmental delays in those same agents in the recipient infant
  2. other agents in human milk do not compensate directly for developmental delays in the production of those same agents, but nevertheless protect the recipient
  3. agents in human milk enhance functions that are poorly expressed in the recipient
  4. agents in human milk change the physiologic state of the intestines from one adapted to intrauterine life to one suited to extrauterine life
  5. some agents in human milk prevent inflammation in the recipient’s gastrointestinal tract
  6. survival of human milk agents in the gastrointestinal tract is enhanced because of delayed production of pancreatic proteases and gastric acid by newborn infants, antiproteases and inhibitors of gastric acid production in human milk, inherent resistance of some human milk agents to proteolysis, and protective binding of other factors in human milk
  7. growth factors in human milk aid in establishing a commensal enteric microflora"

(Text from: Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective.[1])

Immunity

In addition to maternal antibodies, milk contains maternal lymphocytes (antibody-producing B cells. T cells, and natural killer cells). In a mouse model, maternal cytotoxic T cells within milk have been shown to transfer into to the neonatal intestinal Peyer's patches.Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title

The neonatal immune system (innate and adaptive) is immature and still developing, and there is now good evidence that milk contributes to the developmental process, see review.[7]

Milk Production

Development of the breasts and milk production is mainly regulated by the anterior pituitary hormone prolactin (PRL). The release of prolactin is regulated by the hypothalamus prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP)

Prolactin hormone other roles include:

  • regulating follicle stimulating hormone (FSH) effect on the ovary.
  • increased maternal myelination processes during pregnancy.

Prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP) is an 87 amino acid peptide hypothalamus hormone which regulates anterior pituitary release of prolactin.

Prolactin signaling Pathway

In the mammary gland:

  1. Prolactin binds to its receptor (PRLR) and causes them to dimerize.
  2. Receptor-associated tyrosine kinase Jak2 phosphorylates: the prolactin receptor and Stat5a and Stat5b (signal transducers and activators of transcription).
  3. Activated Stat5a and -5b are transported into the nucleus
  4. They specifically bind DNA of target genes (the GAS sequence, TTCNNNGAA).
  5. Induce transcription that promote: proliferation, differentiation, and lactogenesis.

Environmental Contaminants

Environmental components (contaminants) that appear in the milk may depend on the origin (maternal, cow) or the water quality used in formula preparation.

Lead

  • Lead levels in human milk and children's health risk: a systematic review [8]
  • Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother[9] "The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources."
  • Effect of breast milk lead on infant blood lead levels at 1 month of age[10]


Links: Lead | Abnormal Development - Heavy Metals

Organic Pollutants

  • polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB)[11][12]

Abnormalities

Galactorrhoea

Galactorrhoea is the clinical term for inappropriate production of milk that is often associated with anterior pituitary tumours producing excess prolactin. This condition can occur in both females and males.

Galactosaemia

In galactosaemia babies cannot process galactose, a component of lactose. Incidence is about 1 in 40,000 births (about 1-3 cases per year). Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first postnatal week can be life saving.


Necrotizing Enterocolitis

Necrotizing Enterocolitis (NE) is the death of intestinal tissue that occurs postnatally in mainly in premature and low birth weight infants (1 in 2,000 - 4,000 births). The underdeveloped gastointestinal tract appears to be susceptible to bacteria, normally found within the tract, to spread widely to other regions where they damage the tract wall and may enter the bloodstream.

References

  1. 1.0 1.1 Goldman AS. (2000). Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J. Nutr. , 130, 426S-431S. PMID: 10721920
  2. Volpi N, Maccari F, Galeotti F, Peila C, Coscia A, Zampini L, Monachesi C, Gabrielli O & Coppa G. (2020). Human milk glycosaminoglycan composition from women of different countries: a pilot study. J. Matern. Fetal. Neonatal. Med. , 33, 2131-2133. PMID: 30348026 DOI.
  3. Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R & Rodríguez JM. (2013). The human milk microbiota: origin and potential roles in health and disease. Pharmacol. Res. , 69, 1-10. PMID: 22974824 DOI.
  4. Savino F, Liguori SA, Sorrenti M, Fissore MF & Oggero R. (2011). Breast milk hormones and regulation of glucose homeostasis. Int J Pediatr , 2011, 803985. PMID: 21760816 DOI.
  5. Lönnerdal B. (2010). Bioactive proteins in human milk: mechanisms of action. J. Pediatr. , 156, S26-30. PMID: 20105661 DOI.
  6. Manzoni P, Dall'Agnola A, Tomé D, Kaufman DA, Tavella E, Pieretto M, Messina A, De Luca D, Bellaiche M, Mosca A, Piloquet H, Simeoni U, Picaud JC & Del Vecchio A. (2018). Role of Lactoferrin in Neonates and Infants: An Update. Am J Perinatol , 35, 561-565. PMID: 29694997 DOI.
  7. Cacho NT & Lawrence RM. (2017). Innate Immunity and Breast Milk. Front Immunol , 8, 584. PMID: 28611768 DOI.
  8. Koyashiki GA, Paoliello MM & Tchounwou PB. (2010). Lead levels in human milk and children's health risk: a systematic review. Rev Environ Health , 25, 243-53. PMID: 21038758
  9. Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Patison N, Law AJ, Korsch MJ & Salter MA. (1998). Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ. Health Perspect. , 106, 667-74. PMID: 9755144
  10. Ettinger AS, Téllez-Rojo MM, Amarasiriwardena C, Bellinger D, Peterson K, Schwartz J, Hu H & Hernández-Avila M. (2004). Effect of breast milk lead on infant blood lead levels at 1 month of age. Environ. Health Perspect. , 112, 1381-5. PMID: 15471729
  11. Tanabe S & Kunisue T. (2007). Persistent organic pollutants in human breast milk from Asian countries. Environ. Pollut. , 146, 400-13. PMID: 16949712 DOI.
  12. LaKind JS, Berlin CM, Sjödin A, Turner W, Wang RY, Needham LL, Paul IM, Stokes JL, Naiman DQ & Patterson DG. (2009). Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning. Environ. Health Perspect. , 117, 1625-31. PMID: 20019916 DOI.


Journals

Reviews

McGuire E. (2017). Cleft lip and palates and breastfeeding. Breastfeed Rev , 25, 17-23. PMID: 29211381

Cacho NT & Lawrence RM. (2017). Innate Immunity and Breast Milk. Front Immunol , 8, 584. PMID: 28611768 DOI.

Garofalo R. (2010). Cytokines in human milk. J. Pediatr. , 156, S36-40. PMID: 20105664 DOI.

Lapillonne A & Jensen CL. (2009). Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot. Essent. Fatty Acids , 81, 143-50. PMID: 19577914 DOI.

Bombell S & McGuire W. (2009). Early trophic feeding for very low birth weight infants. Cochrane Database Syst Rev , , CD000504. PMID: 19588318 DOI.

McClellan HL, Miller SJ & Hartmann PE. (2008). Evolution of lactation: nutrition v. protection with special reference to five mammalian species. Nutr Res Rev , 21, 97-116. PMID: 19087365 DOI.

Ogra PL. (2009). Developmental aspects of the mucosal immune system: role of external environment, mucosal microflora and milk. Adv. Exp. Med. Biol. , 639, 41-56. PMID: 19227533 DOI.

Wagner CL, Taylor SN & Johnson D. (2008). Host factors in amniotic fluid and breast milk that contribute to gut maturation. Clin Rev Allergy Immunol , 34, 191-204. PMID: 18330727 DOI.

Kent JC. (2007). How breastfeeding works. J Midwifery Womens Health , 52, 564-70. PMID: 17983993 DOI.

Van de Perre P. (2003). Transfer of antibody via mother's milk. Vaccine , 21, 3374-6. PMID: 12850343

Articles

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Search Pubmed: Mammary Gland Development | lactation | human milk | milk | breastfeeding

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Cite this page: Hill, M.A. (2020, July 3) Embryology Normal Development - Milk. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Normal_Development_-_Milk

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